An understanding of the pathogenesis of vertically acquired HIV-1 infections would be aided by a suitable animal model. Feline immunodeficiency virus (FIV), a lentivirus similar to HIV, causes a clinical syndrome comparable to acquired immunodeficiency syndrome, and is also transmitted vertically. The hypothesis to be addressed in this proposal is that vertical transmission of FIV occurs primarily during acute stage maternal infection. The frequency and route of vertical transmission is correlated with the viral burden in maternal tissue and fluids. During Phase I studies, the parameters that govern vertical transmission of FIV will be evaluated in mothers with acute stage FIV infections. Maternal factors that influence vertical FIV transmission (viral burden in blood and milk/colostrum, antibody responses, lymphocyte subset changes, timing of maternal infection in relation to gestation or parturition, and clinical stage of the infection) will be evaluated in cats that are infected at intervals during pregnancy (1st, 2nd, 3rd trimester infections), or immediately post-partum. Fetuses obtained by Caesarian section and kittens allowed to nurse will be monitored for evidence of FIV infection by polymerase chain reaction of fetal tissues and neonatal blood lymphocytes, and by measuring serum anti-FIV antibodies. Additionally, infectious virus in maternal milk and blood, and in cell suspensions obtained from fetal tissues, will be detected by coculture with a feline lymphocyte cell line susceptible to FIV infection. Detection of FIV in maternal and fetal target tissues will be determined by PCR, in situ hybridization and immunocytochemistry. The proposed experiments will shed light on maternal parameters that influence vertical FIV transmission as well as define the predominant route(s) of transmission. During Phase II studies, the risk of vertical transmission of FIV during chronic maternal infection will also be examined, and the risk and frequency of transmission correlated with the maternal factors described. The timing of in utero infection will be determined by obtaining fetuses by C-section at times corresponding to the first second. and third trimester gestation periods. In addition the role of the placenta in vertical FIV transmission will be further examined by evaluating the in vitro susceptibility of cultured feline trophoblast to infection with FIV.